Treg cells suppress osteoclast formation: a new link between the immune system and bone

Mario M Zaiss, Roland Axmann, Jochen Zwerina, Karin Polzer, Eva Gückel, Alla Skapenko, Hendrik Schulze-Koops, Nikki Horwood, Andrew Cope, Georg Schett

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298 Citations (Scopus)


OBJECTIVE: To investigate whether Treg cells can suppress osteoclast differentiation, and to define a new potential link between the immune system and the skeleton.

METHODS: Regulatory CD4+,CD25+,Foxp3+ T cells were isolated and purified from the spleen and cocultured with CD11b+ osteoclast precursor cells isolated from bone marrow. Osteoclastogenesis and bone erosion were assessed by tartrate-resistant acid phosphatase staining and pit resorption assay, respectively. In addition, Transwell experiments and cytokine-blocking experiments were performed to define the mechanisms of interaction between Treg cells and osteoclasts.

RESULTS: CD4+,CD25+,Foxp3+ T cells, but not CD4+,CD25- T cells, dose dependently inhibited macrophage colony-stimulating factor- and RANKL-dependent osteoclast formation. Pit formation was inhibited by up to 80% when Treg cells were added. The blockade of osteoclast formation was not based on the alteration of RANKL/osteoprotegerin balance but was essentially dependent on direct cell-cell contact via CTLA-4. Treg cell-mediated expression of transforming growth factor beta, interleukin-4 (IL-4), and IL-10 contributed but was not essential to the inhibitory effect on osteoclastogenesis.

CONCLUSION: These data show that CD4+,CD25+,Foxp3+ Treg cells suppress osteoclast formation, provide a new link between the immune system and bone, and extend our knowledge on regulation of bone homeostasis by the immune system.

Original languageEnglish
Pages (from-to)4104-4112
Number of pages9
JournalArthritis and Rheumatism
Issue number12
Early online date29 Nov 2007
Publication statusPublished - Dec 2007


  • Animals
  • Antigens, CD/pharmacology
  • Antigens, Differentiation/pharmacology
  • Bone and Bones/cytology
  • CD11 Antigens/metabolism
  • CTLA-4 Antigen
  • Cell Communication/physiology
  • Cell Differentiation/drug effects
  • Cells, Cultured
  • Female
  • Forkhead Transcription Factors/metabolism
  • Immune System/physiology
  • Interleukin-2 Receptor alpha Subunit/metabolism
  • Macrophage Colony-Stimulating Factor/pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Osteoclasts/cytology
  • RANK Ligand/physiology
  • T-Lymphocytes, Regulatory/cytology

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